SFRP4
Basic information
Region (hg38): 7:37905932-38025695
Links
Phenotypes
GenCC
Source:
- Pyle disease (Supportive), mode of inheritance: AR
- Pyle disease (Moderate), mode of inheritance: AR
- Pyle disease (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Pyle disease | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal | 27355534 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (4 variants)
- Pyle metaphyseal dysplasia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SFRP4 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 29 | 34 | ||||
missense | 51 | 57 | ||||
nonsense | 3 | |||||
start loss | 1 | |||||
frameshift | 3 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 3 | 4 | 1 | 8 | ||
non coding | 12 | 12 | ||||
Total | 5 | 3 | 53 | 43 | 7 |
Highest pathogenic variant AF is 0.0000131
Variants in SFRP4
This is a list of pathogenic ClinVar variants found in the SFRP4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
7-37907482-C-G | Benign (Jan 15, 2024) | |||
7-37907486-CTT-C | Uncertain significance (May 29, 2021) | |||
7-37907496-T-A | Inborn genetic diseases | Uncertain significance (Jul 27, 2021) | ||
7-37907501-C-T | Pyle metaphyseal dysplasia • SFRP4-related disorder | Benign (Jan 31, 2024) | ||
7-37907519-G-A | Inborn genetic diseases | Uncertain significance (Apr 07, 2023) | ||
7-37907562-G-T | Pyle metaphyseal dysplasia • SFRP4-related disorder | Benign (Jan 31, 2024) | ||
7-37907573-G-T | Inborn genetic diseases | Uncertain significance (Aug 15, 2022) | ||
7-37907582-G-A | Inborn genetic diseases | Uncertain significance (Aug 16, 2022) | ||
7-37907591-C-T | Uncertain significance (May 12, 2022) | |||
7-37907604-C-T | Inborn genetic diseases | Uncertain significance (Jun 17, 2022) | ||
7-37907605-G-A | SFRP4-related disorder | Benign (May 09, 2023) | ||
7-37907606-G-A | Uncertain significance (Aug 04, 2023) | |||
7-37907609-G-C | Inborn genetic diseases | Uncertain significance (Sep 16, 2021) | ||
7-37907636-C-T | Inborn genetic diseases | Likely benign (Sep 29, 2023) | ||
7-37907653-C-T | Likely benign (Feb 25, 2023) | |||
7-37909611-A-ACTTACTATGGATCTTTTACTAAGCTGATCTCTCCATTTTTCAAC | Uncertain significance (Sep 07, 2022) | |||
7-37909618-A-G | Uncertain significance (Aug 06, 2022) | |||
7-37909624-C-T | Inborn genetic diseases | Uncertain significance (Mar 25, 2024) | ||
7-37909638-A-C | Uncertain significance (Apr 13, 2021) | |||
7-37909673-G-A | Uncertain significance (Jul 19, 2022) | |||
7-37909680-C-T | Uncertain significance (Sep 26, 2022) | |||
7-37909681-C-T | Likely pathogenic (Jul 28, 2023) | |||
7-37909683-GA-G | Benign (Apr 16, 2022) | |||
7-37909692-T-A | Likely benign (Jan 15, 2024) | |||
7-37909698-T-C | Likely benign (Oct 03, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SFRP4 | protein_coding | protein_coding | ENST00000436072 | 6 | 119755 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.0000926 | 0.942 | 125713 | 0 | 35 | 125748 | 0.000139 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.0459 | 210 | 212 | 0.991 | 0.0000114 | 2285 |
Missense in Polyphen | 81 | 85.546 | 0.94686 | 965 | ||
Synonymous | 0.188 | 75 | 77.1 | 0.973 | 0.00000418 | 646 |
Loss of Function | 1.72 | 9 | 16.6 | 0.543 | 7.73e-7 | 180 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000148 | 0.000148 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.000739 | 0.000739 |
European (Non-Finnish) | 0.000106 | 0.000105 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.0000653 | 0.0000653 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927). {ECO:0000250|UniProtKB:Q9JLS4, ECO:0000250|UniProtKB:Q9Z1N6, ECO:0000269|PubMed:12952927}.;
- Disease
- DISEASE: Pyle disease (PYL) [MIM:265900]: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures. {ECO:0000269|PubMed:27355534}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Wnt signaling pathway - Homo sapiens (human);Adipogenesis;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Wnt Signaling Pathway;Wnt Canonical;Wnt Mammals
(Consensus)
Recessive Scores
- pRec
- 0.254
Intolerance Scores
- loftool
- 0.642
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.99
Haploinsufficiency Scores
- pHI
- 0.188
- hipred
- Y
- hipred_score
- 0.557
- ghis
- 0.557
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.121
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sfrp4
- Phenotype
- respiratory system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- positive regulation of receptor internalization;negative regulation of cell population proliferation;response to hormone;positive regulation of gene expression;cell differentiation;negative regulation of Wnt signaling pathway;regulation of BMP signaling pathway;non-canonical Wnt signaling pathway;positive regulation of apoptotic process;negative regulation of DNA-binding transcription factor activity;positive regulation of epidermal cell differentiation;phosphate ion homeostasis;canonical Wnt signaling pathway;bone morphogenesis;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of keratinocyte apoptotic process;negative regulation of non-canonical Wnt signaling pathway;negative regulation of sodium-dependent phosphate transport
- Cellular component
- extracellular space;nucleus;cytoplasm;cell surface
- Molecular function
- protein binding;Wnt-protein binding